PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) is often an incapacitating neural injury most commonly caused by a traumatic blow to the spine, damaging the axons that carry sensory and motor signals between the brain and spinal cord, and in turn, the rest of the body. However, after a contusion to the spinal cord, at least some neuronal fibers above and below the lesion remain intact. Recently, our laboratory and others have introduced new neuroprosthetic approaches in an attempt to restore function by utilizing brain-machine-spinal cord interfaces (BMSIs). These device-based systems use activity-dependent stimulation (ADS) which discriminates neural activity in the intact motor cortex to use as signals to stimulate motor neurons below the spinal cord lesion. Our long-term goal for this research is restoration of impaired motor function in the lower limbs following spinal cord injury. The feasibility of using ADS as a strategy to enhance recovery of function after SCI is supported by the positive results seen in this laboratory demonstrating the effect of ADS in restoring skilled motor function after traumatic brain injury. Thus, the overarching hypothesis of this line of research is that ADS will result in enhanced motor recovery in ambulatory ability after SCI. The proposed project will determine the optimal neurophysiological conditions by which ADS can facilitate enhanced communication between the cerebral cortex and spinal cord motor neurons. The project will address three specific aims: 1) Determine the effects of a contusive spinal cord injury on spinal motor neuron activity, corticospinal coupling, and conduction time in rats 2) determine the optimal spike-stimulus delay for increasing synaptic efficacy in descending motor pathways using an ADS paradigm in an acute, anesthetized rat model of SCI, and 3) determine whether spike-triggered ISMS results in improved motor performance in an ambulatory rat model of SCI. We will test these aims using acute and chronic neurologic recording and stimulating techniques in both anesthetized and awake, behaving healthy and SCI rodents. The project is significant because, if realized, this approach may augment concomitant physical and occupational therapy and result in improved functional abilities. Ultimately, patients may could regain voluntary movement due to increased synaptic efficacy in corticospinal fibers.